Epilepsy is a general term describing brain disorders that are characterized by the occurrence of seizures. Epilepsy affects millions of people worldwide, and over 2.5 million individuals in the United States. For the purposes of clinical assessment, it is useful to classify patients according to the type of seizure the patient experiences.
As described in The Pharmacological Basis of Therapeutics, seizures can occur periodically or unpredictably. (Goodman, L. S., et al., Goodman & Gilman's The pharmacological basis of therapeutics. 9th ed. 1996, New York: McGraw-Hill Health Professions Division. xxi, 1905, Chapter 20). Over 30 types of epileptic seizures have been described, and they can be generally classified into two groups—partial seizures (beginning focally in a cortical site) or generalized seizures (involving both brain hemispheres from the outset). Partial seizures include simple partial, complex partial and partial with secondarily generalized tonic-clonic seizures. Generalized seizures include absence, myoclonic, atonic, tonic, clonic, and tonic-clonic (grand mal) seizures.
Hundreds of epileptic syndromes have been defined as disorders characterized by specific symptoms that include epileptic seizures. These epileptic syndromes include, but are not limited to, absence epilepsy, psychomotor epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, occipital lobe epilepsy, parietal lobe epilepsy, Lennox-Gastaut syndrome, Rasmussen's encephalitis, childhood absence epilepsy, Ramsay Hunt syndrome type II, benign epilepsy syndrome, benign infantile encephalopathy, benign neonatal convulsions, early myoclonic encephalopathy, progressive epilepsy, and infantile epilepsy.
A patient may suffer from any combination of different types of seizures. Partial seizures are the most common type, and account for approximately 60% of all seizure types. Regardless of the type of epilepsy, seizures significantly limit the autonomy of the patient.
It is believed that the characteristic seizures of epilepsy are caused by the disordered, synchronous and rhythmic firing of brain neurons. The neurons can fire at up to four times their normal rate. As a result, epileptic seizures are an over stimulation of the normal neuronal processes that control brain function.
Anti-epileptic drugs are available for treating epilepsies, but these agents have a number of shortcomings. For instance, the agents are often poorly soluble in aqueous and biological fluids or are extremely hygroscopic. Of even greater importance is that patients often become refractory to a drug over time. In addition, many anti-epileptic agents cause unwanted side effects, neurotoxicities, and drug interactions. Even while being treated with one or a combination of the anti-epileptic drugs currently in clinical use, 30% of epileptic patients still experience seizures. As more anti-epileptic drugs are developed, the clinician will have expanded pharmaceutical options when designing an effective treatment protocol for each patient.
U.S. Pat. No. 5,677,349 to Gilad et al. discloses methods for treating neurotrauma or neurodegenerative disease in a human by administering agmatine (4-aminobutylguanidine). Neurotrauma and neurodegeneration are terms denoting the loss of cells in the brain resulting from an external trauma or an external invasive procedure. Examples of neurodegeneration disorders include, for instance, Alzheimer's disease and Parkinson's disease, which result from the decline of neurons in the substantia nigra that produce dopamine. The neurodegenerative disorder, amyotrophic lateral sclerosis (ALS), results from the degeneration of neurons that control voluntary movement. Treatment modalities for epilepsy, however, attenuate neuronal activity, i.e., regulate the over stimulation of the neuronal processes that control brain function rather than treat cell death. Thus, it is believed that Gilad et al. have not recognized the use of agmatine in the treatment or prevention of epilepsy, seizure, and other electroconvulsive disorders.
Accordingly a continuing need exists for pharmaceutical compositions that treat or prevent epilepsy and its associated symptoms with minimal side-effects.